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OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids
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OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids
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Journal Article
OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids
2014
Overview
The presence of nucleic acids in the cytosol alerts the cell to viral infection or damaged self. The oligoadenylate synthase (OAS) proteins and cyclic GMP–AMP synthase (cGAS) are enzymes that detect this danger and promote antiviral immunity. Recent structural studies reveal that these enzymes have a common mechanism of action and probably the same evolutionary origin.
Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP–AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2′–5′-linked second messenger molecules, which — through distinct mechanisms — have crucial antiviral functions. 2′–5′-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2′–5′-linked cGAMP activates downstream signalling pathways to induce
de novo
antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
2',5'-Oligoadenylate Synthetase - genetics
/ 2',5'-Oligoadenylate Synthetase - immunology
/ Acids
/ Adenine Nucleotides - genetics
/ Adenine Nucleotides - immunology
/ Cytosol
/ Endoribonucleases - biosynthesis
/ Endoribonucleases - genetics
/ Enzymes
/ Humans
/ Kinases
/ Nucleotides, Cyclic - genetics
/ Nucleotidyltransferases - genetics
/ Nucleotidyltransferases - immunology
/ Oligoribonucleotides - genetics
/ Oligoribonucleotides - immunology
/ progress
/ Proteins
/ Second Messenger Systems - genetics
/ Second Messenger Systems - immunology
/ Structure-function relationships
/ Viruses
